4-Methylmorpholine → HCID 178501385, compound

HRID 413008Notes

Reaction equation

HRID 413008 reaction equation
[NH:1]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C@@H:2]([C:27](O)=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:21])[CH3:20])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10].CN1CCOCC1.[NH2:44][C@H:45]([C:53]([NH:55][C@H:56]([C:69]([O:71][CH3:72])=[O:70])[CH2:57][C:58]1[CH:63]=[CH:62][C:61]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[CH:60][CH:59]=1)=[O:54])[C@@H:46]([CH3:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49]>CN1C(=O)CCC1.C(Cl)(Cl)Cl>[NH:1]([C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C@@H:2]([C:27]([NH:44][C@@H:45]([C:53]([NH:55][C@@H:56]([C:69]([O:71][CH3:72])=[O:70])[CH2:57][C:58]1[CH:63]=[CH:62][C:61]([O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[CH:60][CH:59]=1)=[O:54])[C@H:46]([CH3:52])[O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:28])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:26])[NH:8][S:9]([C:12]1[C:24]([CH3:25])=[C:23]2[C:17]([O:18][C:19]([CH2:22]2)([CH3:20])[CH3:21])=[C:15]([CH3:16])[C:13]=1[CH3:14])(=[O:11])=[O:10]

Participants

6

Reactant 3

HCID 79724-MethylmorpholineHCID 131721155HCID 131721155, compoundHCID 178427603HCID 178427603, compound

Product 1

HCID 178501385HCID 178501385, compoundYield 86%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
-10 °C

Procedure

A clear solution of 3.73 g (7.08 mmoles) of Boc-D-Arg(Pbf)-OH (Bachem Feinchemikalien, cat. No A-3750) in 75 ml of dry NMP, comprising 0.85 ml (7.79 mmoles) of NMM was chilled to −10° C. under shaking. Then, 1.02 ml (7.79 mmoles) of IBCF diluted in 6 ml of CHCl3 were added drop-wise. After 30 minutes, a solution of 2.88 g (7.08 mmoles) of H-L-Thr(tBu)-L-Tyr(tBu)-OMe in 75 ml of CHCl3 was added drop-wise in 20 minutes. The reaction mixture was kept for 2 h at 0° C. and overnight at room temperature. The solvent was evaporated under vacuum and the crude material was purified by flash chromatography on silica gel column, using a mixture of AcOEt-hexane as eluent. There were thus obtained 5.58 g (6.08 mmoles, yield 86%) of Boc-D-Arg(Pbf)-D-Thr(tBu)-D-Tyr(tBu)-OMe, as pure oil (TLC and RP-HPLC).

Workup

  1. additionwere added drop-wise
  2. waitThe reaction mixture was kept for 2 h at 0° C. and overnight at room temperature
  3. customThe solvent was evaporated under vacuum
  4. customthe crude material was purified by flash chromatography on silica gel column
  5. additiona mixture of AcOEt-hexane as eluent

Sources & evidence

ORD record
ord-f77fc05e2f2f43489f8e5a0db2ec81b3
Source dataset
uspto-grants-2003_05
Patent number
US06566077B1

Reaction notes

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